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Epicutaneous immunization with type II collagen inhibits both onset and progression of chronic collagen-induced arthritis
- Source :
- PLoS ONE, PLoS ONE, Vol 2, Iss 4, p e387 (2007)
- Publication Year :
- 2007
-
Abstract
- Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis.
- Subjects :
- General Science & Technology
Dermatology/Skin and Systemic Disease
T cell
T-Lymphocytes
Immunology/Immunomodulation
lcsh:Medicine
Arthritis
Immunology/Autoimmunity
chemical and pharmacologic phenomena
Immunoglobulin E
Antibodies
Interferon-gamma
Mice
Immune system
Antigen
MD Multidisciplinary
medicine
Animals
Interferon gamma
IL-2 receptor
lcsh:Science
Collagen Type II
Rheumatology/Rheumatoid Arthritis
Rheumatology/Autoimmunity, Autoimmune, and Inflammatory Diseases
Cell Proliferation
Skin
Multidisciplinary
biology
business.industry
lcsh:R
medicine.disease
Arthritis, Experimental
medicine.anatomical_structure
Mice, Inbred DBA
Immunology
biology.protein
Disease Progression
lcsh:Q
Antibody
business
medicine.drug
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 2
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....f526e63e7f49e20bc900c4cca3acf676